Abstract
Alport syndrome (AS) is a hereditary progressive nephropathy characterized by hematuria, ultrastructural lesions of the glomerular basement membrane, ocular lesions and sensorineural hearing loss. Germline mutations of COL4A5 are associated with X-linked AS with an extreme phenotypic heterogeneity. Here, we investigated a Chinese family with Alport syndrome. The proband was a 9-year-old boy with hematuria and proteinuria. Based on the test results of renal biopsy and immunofluorescence, the proband was initially diagnosed as IgA nephropathy and the treatment was recommended accordingly. Meanwhile, we found that the treatment outcome was poor. Therefore, for proper clinical diagnosis and appropriate treatment, targeted exome-based next-generation sequencing has been undertaken. We identified a novel hemizygous single nucleotide deletion c.1902delA in COL4A5 gene. Segregation analysis identified that this novel mutation is co-segregated among the affected family members but absent in unaffected family members. The clinical diagnosis of the proband was revised as AS accompanied by IgA nephropathy, which has been rarely reported. Our findings demonstrated the significance of the application of Genetic screening, expanded the mutation spectrum of COL4A5 associated AS patients with atypical renal phenotypes and provided a good lesson to be learned from our detour during the diagnosis.
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The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
This work was supported by the Key Research and Development Program of Hunan Province in China (2018SK2139). The authors thank all colleagues who processed medical records, managed patients, performed renal biopsies, and assisted with follow-up. We would like to express our gratitude to the patients and their family members, who made this study possible.
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Compliance and ethics The author(s) declare that they have no conflict of interest. The study followed the tenets of the Declaration of Helsinki and was approved by the institutional review board of BGI and Children s Hospital of Hunan Province, China. Informed consents were obtained from all the family members.
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Li, Z., Zhu, P., Huang, H. et al. Identification of a novel COL4A5 mutation in the proband initially diagnosed as IgAN from a Chinese family with X-linked Alport syndrome. Sci. China Life Sci. 62, 1572–1579 (2019). https://doi.org/10.1007/s11427-018-9545-3
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DOI: https://doi.org/10.1007/s11427-018-9545-3